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At least 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Computer Model Used to Help Customize Medicine

Dr. Radhakrishnan, a researcher at the NASA Glenn Research Center, in collaboration with biomedical researchers at the Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital, is developing computational models of human physiology that quantitate metabolism and its regulation, in both healthy and pathological states. These models can help predict the effects of stresses or interventions, such as drug therapies, and contribute to the development of customized medicine. Customized medical treatment protocols can give more comprehensive evaluations and lead to more specific and effective treatments for patients, reducing treatment time and cost. Commercial applications of this research may help the pharmaceutical industry identify therapeutic needs and predict drug-drug interactions. Researchers will be able to study human metabolic reactions to particular treatments while in different environments as well as establish more definite blood metabolite concentration ranges in normal and pathological states. These computational models may help NASA provide the background for developing strategies to monitor and safeguard the health of astronauts and civilians in space stations and colonies. They may also help to develop countermeasures that ameliorate the effects of both acute and chronic space exposure.

Stauber, Laurel J.↗
NASA NTRS2004

Calibration Experiments Conducted for Noninvasive Blood Glucose Sensing Through the Eye

There are more than 16 million diabetics in the United States and more than 100 million worldwide. Diabetes can lead to severe complications over time such as blindness, renal and cardiovascular diseases, and peripheral neuropathy in the limbs. Poor blood circulation in diabetics can lead to gangrene and the subsequent amputation of extremities. In addition, this pathology is the fourth leading cause of death in the United States. The most effective way to manage diabetes is frequent blood glucose monitoring performed by the patients themselves. However, because of pain, inconvenience, and the fear of developing infections from finger-prick blood tests or implants, many patients monitor their blood glucose levels less frequently than is recommended by their physicians. Therefore, a noninvasive, painless, and convenient method to monitor blood glucose would greatly benefit diabetics. Likewise, detecting, preventing, and treating the untoward effects of prolonged space travel (e.g., a human mission to Mars) in real-time requires the development of noninvasive diagnostic technologies that are compact and powerful. As a "window to the body," the eye offers the opportunity to use light in various forms to detect ocular and systemic abnormalities long before clinical symptoms appear and to help develop preventative and therapeutic countermeasures early. The noninvasive feature of these technologies permits frequent repetition of tests, enabling an evaluation of the response to therapy.

Ansari, Rafat R.↗
NASA NTRS2005

By Different Cellular Mechanisms, Lymphatic Vessels Sprout by Endothelial Cell Recruitment Whereas Blood Vessels Grow by Vascular Expansion

The development of effective vascular therapies requires the understanding of all modes of vessel formation contributing to vasculogenesis, angiogenesis (here termed hemangiogenesis) and lymphangiogenesis. We show that lymphangiogenesis proceeds by blind-ended vessel sprouting via recruitment of isolated endothelial progenitor cells to the tips of growing vessels, whereas hemangiogenesis occurs by non-sprouting vessel expansion from the capillary network, during middevelopment in the quail chorioallantoic membrane (CAM). Blood vessels expanded out of capillaries that displayed transient expression of alpha smooth muscle actin (alphaSMA), accompanied by mural recruitment of migratory progenitor cells expressing SMA. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptors VEGFR-1 and VEGFR-2, alphaSMA (expressed on CAM blood vessels but not on lymphatics), homeobox transcription factor Prox-1 (specific to CAM lymphatic endothelium), and the quail hematopoetic/vascular marker, QH-1. Expression of VEGFR-1 was highly restricted to blood vessels (primarily capillaries). VEGFR-2 was expressed intensely in isolated hematopoietic cells, lymphatic vessels and moderately in blood vessels. Prox-1 was absent from endothelial progenitor cells prior to lymphatic recruitment. Although vascular endothelial growth factor-165 (VEGF(sub 165)) is a key regulator of numerous cellular processes in hemangiogenesis and vasculogenesis, the role of VEGF(sub 165) in lymphangiogenesis is less clear. Exogenous VEGF(sub 165) increased blood vessel density without changing endogenous modes of vascular/lymphatic vessel formation or marker expression patterns. However, VEGF(sub 165) did increase the frequency of blood vascular anastomoses and strongly induced the antimaturational dissociation of lymphatics from blood vessels, with frequent formation of homogeneous lymphatic networks.

Parsons-Wingerter, Patricia↗
NASA NTRS2004

Neuro-vestibular and Sensory-motor Challenges Associated with NASA Mission Architectures for Moon and Mars

Data from six-month low Earth orbit space flight missions suggest that that substantial neuro-vestibular/sensory-motor adaptation will take place during six-month transit missions to and from Mars. Could intermittent or continuous artificial gravity be used to offset these effects? To what degree would the effects of adaptation to this rotational cure affect its potential benefits? Also, little information exists regarding the gravity thresholds for maintaining functional performance of complex sensory-motor tasks such as balance control and locomotion. Will sensory-motor coordination systems adapt to 30- 90 days of 1/6 g on the lunar surface or 18 months of 3/8 g on the Martian surface? Would some form of gravity replacement therapy be required on the surface? And, will transitions between 0 g and 1/6 g or 1/3 g present as great a challenge to the vestibular system as transitions between 0 g and 1 g? Concerted research and development efforts will be required to obtain the answers.

Paloski, William H.↗
NASA NTRS2004

Lessons from Immune 1-3: what did we learn and what do we need to do in the future?

Sprague-Dawley rats were subjected to three 8-to-10 day space flights on the Space Shuttle. Housed in NASA's Animal Enclosure Modules, rats were flown to test the hypotheses that therapy with pegylated interleukin-2 or insulin-like growth factor-1 would ameliorate some of the effects of space flight on the immune system. As part of these experiments, we measured body and organ weights, blood cell differentials, plasma corticosterone, macrophage colony forming units, lymphocyte mitogenic, super-antigenic and interferon-gamma responses, bone marrow cell and peritoneal macrophage cytokine secretion and bone strength and mass. This paper compares some of the immunophysiological parameters of the control animals used in the Immune1-3 flight series and presents data from an animal infection model for use during space flight.

short duration↗
NASA NTRS2005

Photons, clocks, and consciousness

Light profoundly impacts human consciousness through the stimulation of the visual system and powerfully regulates the human circadian system, which, in turn, has a broad regulatory impact on virtually all tissues in the body. For more than 25 years, the techniques of action spectroscopy have yielded insights into the wavelength sensitivity of circadian input in humans and other mammalian species. The seminal discovery of melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, has provided a significant turning point for understanding human circadian phototransduction. Action spectra in humans show that the peak wavelength sensitivity for this newly discovered sensory system is within the blue portion of the spectrum. This is fundamentally different from the three-cone photopic visual system, as well as the individual rod and cone photoreceptor peaks. Studies on rodents, nonhuman primates, and humans indicate that despite having a different wavelength fingerprint, these classic visual photoreceptors still provide an element of input to the circadian system. These findings open the door to innovations in light therapy for circadian and affective disorders, as well as possible architectural light applications.

Review↗
NASA NTRS2005

A WOUND CARE AND INTRAVENOUS ACCESS SUMMIT FOR ON-ORBIT CARE

Wound care issues and the ability to establish intravenous (IV) access among injured or ill crew members are a source of concern for NASA flight surgeons. Indeed, the microgravity environment and the remote nature of the International Space Station (ISS) pose unique challenges in diagnosing and treating an injured astronaut. Therefore, it is necessary to identify and adapt the best evidence based terrestrial practices regarding wound care, hemostasis, and IV access for use on the ISS. Methods: A panel of consultants was convened to evaluate the adequacy of the current ISS in-flight medical system for diagnosis and treatment of wounds and establishing IV access by a nonclinician crew medical officer. Participants were acknowledged experts in terrestrial wound care and/or operational medicine. Prior to the meeting, each panelist was encouraged to participate in a pre-summit online forum. Results: Eight external experts participated in a face-to-face meeting held at NASA-Johnson Space Center. Recommendations were made to augment the space station pharmacopoeia, as well as current wound care diagnostic, therapeutic, and deorbit criteria protocols. Additionally, suggestions were offered regarding IV access techniques and devices for use in the microgravity environment. Discussion: The results of the expert panel provide an evidence-based approach to the diagnosis and care of wounds in an injured astronaut on aboard the ISS. The results of the panel underscored the need for further research in wound therapy and IV access devices.

Scheuring, R.↗
NASA NTRS2005

High Frequency QRS ECG Accurately Detects Cardiomyopathy

High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing RAZ scoring is a simple, accurate and inexpensive screening technique for cardiomyopathy. Although HF QRS ECG is highly sensitive for cardiomyopathy, its specificity may be compromised in patients with cardiac pathologies other than cardiomyopathy, such as uncomplicated coronary artery disease or multiple coronary disease risk factors. Further studies are required to determine whether HF QRS might be useful for monitoring cardiomyopathy severity or the efficacy of therapy in a longitudinal fashion.

Schlegel, Todd T.↗
NASA NTRS2006

Update On the Status of the FLUKA Monte Carlo Transport Code*

The FLUKA Monte Carlo transport code is a well-known simulation tool in High Energy Physics. FLUKA is a dynamic tool in the sense that it is being continually updated and improved by the authors. We review the progress achieved since the last CHEP Conference on the physics models, some technical improvements to the code and some recent applications. From the point of view of the physics, improvements have been made with the extension of PEANUT to higher energies for p, n, pi, pbar/nbar and for nbars down to the lowest energies, the addition of the online capability to evolve radioactive products and get subsequent dose rates, upgrading of the treatment of EM interactions with the elimination of the need to separately prepare preprocessed files. A new coherent photon scattering model, an updated treatment of the photo-electric effect, an improved pair production model, new photon cross sections from the LLNL Cullen database have been implemented. In the field of nucleus-- nucleus interactions the electromagnetic dissociation of heavy ions has been added along with the extension of the interaction models for some nuclide pairs to energies below 100 MeV/A using the BME approach, as well as the development of an improved QMD model for intermediate energies. Both DPMJET 2.53 and 3 remain available along with rQMD 2.4 for heavy ion interactions above 100 MeV/A. Technical improvements include the ability to use parentheses in setting up the combinatorial geometry, the introduction of pre-processor directives in the input stream. a new random number generator with full 64 bit randomness, new routines for mathematical special functions (adapted from SLATEC). Finally, work is progressing on the deployment of a user-friendly GUI input interface as well as a CAD-like geometry creation and visualization tool. On the application front, FLUKA has been used to extensively evaluate the potential space radiation effects on astronauts for future deep space missions, the activation dose for beam target areas, dose calculations for radiation therapy as well as being adapted for use in the simulation of events in the ALICE detector at the LHC.

Ferrari, A.↗
NASA NTRS2004

Neuro-vestibular and Sensory-motor Challenges Associated with NASA Mission Architectures for Moon and Mars

Data from six-month low Earth orbit space flight missions suggest that that substantial neuro-vestibuladsensory-motor adaptation will take place during six-month transit missions to and from Mars. Could intermittent or continuous artificial gravity be used to offset these effects? To what degree would the effects of adaptation to this rotational cure affect its potential benefits? Also, little information exists regarding the gravity thresholds for maintaining functional performance of complex sensory-motor tasks such as balance control and locomotion. Will sensory-motor coordination systems adapt to 30-90 days of 1/6 g on the lunar surface or 18 months of 3/8 g on the Martian surface? Would some form of gravity replacement therapy be required on the surface? And, will transitions between 0 g and 1/6 g or 1/3 g present as great a challenge to the vestibular system as transitions between 0 g and 1 g? Concerted research and development efforts will be required to obtain the answers.

Paloski, William H.↗
NASA NTRS2004

Bioavailability and Pharmacodynamics of Promethazine on Long Duration Missions to the International Space Station

Space motion sickness (SMS) is often treated in space with promethazine (PMZ). Common side effects of PMZ administration (50 mg intramuscular) on the ground are drowsiness and impaired cognitive performance. Anecdotal reports indicate that these effects are absent or less pronounced in space. This suggests that the availability of PMZ to the body (bioavailability) and/or the response of the body to PMZ (pharmacodynamics) may change during space flight. Opportunities for clinical research in space are limited. The study described here is our response to a NASA Research Announcement for proposals for flight-based research needed to improve, or answer specific questions about, diagnosis and therapy during space flight, and post-flight rehabilitation. We propose here to evaluate noninvasive methods for determining the bioavailability and pharmacodynamics of PMZ. The specific objectives of the proposed research are to 1) compare pharmacokinetic and pharmacodynamic parameters of PMZ, estimated from saliva and plasma levels after administration of PMZ, 2) estimate the relative bioavailability of the three dosage forms of PMZ that are often administered to control motion sickness symptoms in space, and 3) establish the dose-response relationship of PMZ. We will estimate the bioavailability of an intramuscular injection (IM), oral tablet, and rectal suppository of PMZ in noma1 subjects during ambulatory and antiorthostatic bed rest (ABR) conditions using novel stable isotope techniques. We will compare and contrast the bioavailability of PMZ during normal and microgravity conditions to examine changes in drug absorption and bioavailability during microgravit. Results of this study will validate methods for an approved in-flight investigation with this medication awaiting an opportunity for manifestation..

Putcha, Lakshmi↗
NASA NTRS2007

Association between Randall's Plaque and Calcifying Nanoparticles

Randall's plaques, first described by Alexander Randall in the 1930s, are small subepithelial calcifications in the renal papillae (RP) that also extend deeply into the renal medulla. Despite the strong correlation between the presence of these plaques and the formation of renal stones, the precise origin and pathogenesis of Randall s plaque formation remain elusive. The discovery of calcifying nanoparticles (CNP) and their detection in many calcifying processes of human tissues has raised hypotheses about their possible involvement in renal stone formation. We collected RP and blood samples from 17 human patients who had undergone laparoscopic nephrectomy due to neoplasia. Homogenized RP tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis were performed on fixed RP samples. Immunohistochemical staining (IHS) was applied on the tissue samples using CNP-specific monoclonal antibody (mAb). Randall s plaques were visible on gross inspection in 11 out of 17 collected samples. Cultures of all serum samples and 13 tissue homogenates had CNP growth within 4 weeks. SEM revealed spherical apatite formations in 14 samples, with calcium and phosphate peaks detected by EDS analysis. IHS was positive in 9 out of 17 samples. A strong link was found between the presence of Randall s plaques and the detection of CNP, also referred to as nanobacteria. These results suggest new insights into the etiology of Randall's plaque formation, and will help us understand the pathogenesis of stone formation. Further studies on this topic may lead us to new approaches on early diagnosis and novel medical therapies of kidney stone formation.

Ciftcioglu, Neva↗
NASA NTRS2005

Artificial Gravity: Will it Preserve Bone Health on Long-Duration Missions?

Prolonged microgravity exposure disrupts bone, muscle, and cardiovascular homeostasis, sensory-motor coordination, immune function, and behavioral performance. Bone loss, in particular, remains a serious impediment to the success of exploration-class missions by increasing the risks of bone fracture and renal stone formation for crew members. Current countermeasures, consisting primarily of resistive and aerobic exercise, have not yet proven fully successful for preventing bone loss during long-duration spaceflight. While other bone-specific countermeasures, such as pharmacological therapy and dietary modifications, are under consideration, countermeasure approaches that simultaneously address multiple physiologic systems may be more desirable for exploration-class missions, particularly if they can provide effective protection at reduced mission resource requirements (up-mass, power, crew time, etc). The most robust of the multi-system approaches under consideration, artificial gravity (AG), could prevent all of the microgravity-related physiological changes from occurring. The potential methods for realizing an artificial gravity countermeasure are reviewed, as well as selected animal and human studies evaluating the effects of artificial gravity on bone function. Future plans for the study of the multi-system effects of artificial gravity include a joint, cooperative international effort that will systematically seek an optimal prescription for intermittent AG to preserve bone, muscle, and cardiovascular function in human subjects deconditioned by 6 degree head-down-tilt-bed rest. It is concluded that AG has great promise as a multi-system countermeasure, but that further research is required to determine the appropriate parameters for implementation of such a countermeasure for exploration-class missions.

Davis-Street, Janis↗
NASA NTRS2000

Gas storage using fullerene based adsorbents

This invention is directed to the synthesis of high bulk density high gas absorption capacity adsorbents for gas storage applications. Specifically, this invention is concerned with novel gas absorbents with high gravimetric and volumetric gas adsorption capacities which are made from fullerene-based materials. By pressing fullerene powder into pellet form using a conventional press, then polymerizing it by subjecting the fullerene to high temperature and high inert gas pressure, the resulting fullerene-based materials have high bulk densities and high gas adsorption capacities. By pre-chemical modification or post-polymerization activation processes, the gas adsorption capacities of the fullerene-based adsorbents can be further enhanced. These materials are suitable for low pressure gas storage applications, such as oxygen storage for home oxygen therapy uses or on-board vehicle natural gas storage. They are also suitable for storing gases and vapors such as hydrogen, nitrogen, carbon dioxide, and water vapor.

Loutfy, Raouf O.↗
NASA NTRS2004

Gravity-independent constant force resistive exercise unit

This invention describes a novel gravity-independent exercise unit designed for use in microgravity, or on the ground, as a means by which to counter muscle atrophy and bone degradation due to disuse or underuse. Modular resistive packs comprising constant torque springs provide constant force opposing the withdrawal of an exercise cable from the device. In addition to uses within the space program, the compact resistive packs of the CFREU allow the unit to be small enough for easy use as a home gym for personal use, or as a supplement for rehabilitation programs. Resistive packs may be changed conveniently out of the CFREU according to the desired exercise regimen. Thus, the resistive packs replace the need for expensive, heavy, and bulky traditional weight plates. The CFREU may be employed by hospitals, rehabilitation and physical therapy clinics, and other related professional businesses.

Colosky, Jr., Paul E.↗
NASA NTRS2008

Radio-sensitization of Prostate Cancer Cells by Monensin Treatment and its associated Gene Expression Profiling Changes

Radio-resistant or recurrent prostate cancer represents a serious health risk for approximately 20%-30% of patients treated with primary radiation therapy for clinically localized prostate cancer. Here, we investigated the effect of monensin on sensitizing radiation mediated cell killing of two radio-resistant prostate cell lines Lncap (P53+ and AR+) and PC3 (P53- and AR-). Treatment with monensin alone (5 micromoles-20 micromoles) showed a significant direct cell killing of Lncap (10-30%), but not PC3 cells. Monensin was also shown to successfully sensitize Lncap cells to X-ray radiation (2Gy-10Gy) mediated cell death, up to 50% of killing with the combined treatment. To better understand the mechanisms of radio-resistance of these two cell lines and their different response to monensin, the apoptosis related gene expression profiles in both cell lines were analyzed using cDNA PCR array. Without any treatment, PC3 showed a much higher expression level of antiapoptosis genes than Lncap in the BCL2 family, the caspase/card family and the TNF ligand/receptor family. At 2 hr after 20 micormolar monensin treatment alone, only the TRAF and CIDE family showed a greater induction in Lncap cells than in PC3. Exposures to 10 Gy X-rays alone of Lncap cells significantly induced gene expression levels in the death and death receptor domain family, the TNF ligand and receptor family, and apoptotic group of BCL2 family; whereas exposures of PC3 induced only the expression of genes in the anti-apoptosis group of CASP and CARD family. Furthermore, we selectively suppressed the expression of several anti-apoptosis genes (BCL-xl, Bcl2A1, BIRC2, BIRC3 and CASP2) in PC3 cells by using the siRNA treatment. Exposure to 10Gy X-rays alone showed an enhanced cell killing (about 15%) in BCL-x1 silenced cells, but not in cells with siRNA treatment targeting other anti-apoptosis genes. We also exposed PC3 cells to protons in the Bragg peak region to compare the effectiveness of cell killing of X-rays. Interestingly, in comparison to X-rays, protons significantly reduced the gene expression in the anti-apoptosis family, suggesting that proton treatment may be more effective for PC3 cells. As a conclusion, monensin was found to sensitize Lncap cells, but not PC3, and over-expression of Bcl-xl cells may be responsible for the radio- or chemo-resistance characteristics of PC3 cells.

Zhang Ye↗
NASA NTRS2006

The FLUKA Code: An Overview

FLUKA is a multipurpose Monte Carlo code which can transport a variety of particles over a wide energy range in complex geometries. The code is a joint project of INFN and CERN: part of its development is also supported by the University of Houston and NASA. FLUKA is successfully applied in several fields, including but not only, particle physics, cosmic ray physics, dosimetry, radioprotection, hadron therapy, space radiation, accelerator design and neutronics. The code is the standard tool used at CERN for dosimetry, radioprotection and beam-machine interaction studies. Here we give a glimpse into the code physics models with a particular emphasis to the hadronic and nuclear sector.

Ballarini, F.↗
NASA NTRS2008

Grazing-Incidence Neutron Optics based on Wolter Geometries

The feasibility of grazing-incidence neutron imaging optics based on the Wolter geometries have been successfully demonstrated. Biological microscopy, neutron radiography, medical imaging, neutron crystallography and boron neutron capture therapy would benefit from high resolution focusing neutron optics. Two bounce optics can also be used to focus neutrons in SANS experiments. Here, the use of the optics would result in lower values of obtainable scattering angles. The high efficiency of the optics permits a decrease in the minimum scattering vector without lowering the neutron intensity on sample. In this application, a significant advantage of the reflective optics over refractive optics is that the focus is independent of wavelength, so that the technique can be applied to polychromatic beams at pulsed neutron sources.

Gubarev, M. V.↗